It is 50 years since The Structure of Scientific Revolutions presented a radically different perspective on the way scientists carry out their work. Most readers of this book would have been familiar with the scientific method, which sets out the way science is supposed to work. But the textbook "scientific method" underplays the creative contributions provided by scientists, and Thomas Kuhn knew that the history of science provides abundant evidence showing that human factors deserve a much higher profile in our thinking. Yet he knew his book was iconoclastic:
"Kuhn was not at all confident about how Structure would be received. He had been denied tenure at Harvard University in Cambridge, Massachusetts, a few years before, and he wrote to several correspondents after the book was published that he felt he had stuck his neck "very far out". Within months, however, some people were proclaiming a new era in the understanding of science. One biologist joked that all commentary could now be dated with precision: his own efforts had appeared "in the year 2 B.K.", before Kuhn. A decade later, Kuhn was so inundated with correspondence about the book that he despaired of ever again getting any work done."
Cover for the 3rd edition (source here)
After two decades, "Structure had achieved blockbuster status". Sales were approaching a million copies and numerous foreign-language editions had been published. "The book became the most-cited academic work in all of the humanities and social sciences between 1976 and 1983." This last statistic is the key to understanding its subsequent fortune: the book was like a magnet to sociologists of science because its message was about the human face of science. Although Kuhn started his career as a physicist, he crossed over to the history and philosophy of science. What he had to say was less appealing to the science community.
The keyword for Kuhn was "paradigm". Originally, the word was used to refer to a defining example or pattern or model. Later, it was associated with a theoretical framework for understanding an aspect of the world around us. Kuhn's approach drew on both these meanings and gave them new depths.
"[Kuhn] separated his intended meanings into two clusters. One sense referred to a scientific community's reigning theories and methods. The second meaning, which Kuhn argued was both more original and more important, referred to exemplars or model problems, the worked examples on which students and young scientists cut their teeth. As Kuhn appreciated from his own physics training, scientists learned by immersive apprenticeship; they had to hone what Hungarian chemist and philosopher of science Michael Polanyi had called "tacit knowledge" by working through large collections of exemplars rather than by memorizing explicit rules or theorems. More than most scholars of his era, Kuhn taught historians and philosophers to view science as practice rather than syllogism."
Kuhn analysis was, and continues to be, a big influence on my own thinking. His first contribution was to show that incremental progress in science is only part of the story. It is a major part, and it tends to dominate the thinking of most working scientists. Kuhn explained how anomalies in theory are approached: normal science sees anomalies as problems to be solved incrementally whereas revolutionary science sees anomalies as pointers to another, better way of approaching the evidence and defining the problems. Finding that better way leads to a new conceptual framework and constitutes a scientific revolution.
Having contributed this understanding of revolutions in science, Kuhn also cast light on some of the extraordinary tussles that ensue before and after these revolutions. There are strongly worded disputes; scientists display emotion; people feel affronted! Kuhn explained that people who have developed different paradigms of understanding the evidence find it very difficult to communicate with each other. This is relevant to the mixed reception given to Kuhn's book: for some, it was door into a new appreciation of science, but it offended many operating within the positivist paradigm, as Kuhn made "a break with several key positivist doctrines".
"Most controversial was Kuhn's claim that scientists have no way to compare concepts on either side of a scientific revolution. For example, the idea of 'mass' in the Newtonian paradigm is not the same as in the Einsteinian one, Kuhn argued; each concept draws meaning from separate webs of ideas, practices and results. If scientific concepts are bound up in specific ways of viewing the world, like a person who sees only one aspect of a Gestalt psychologist's duck-rabbit figure, then how is it possible to compare one concept to another? To Kuhn, the concepts were incommensurable: no common measure could be found with which to relate them, because scientists, he argued, always interrogate nature through a given paradigm."
An ambiguous figure in which the brain switches between seeing a rabbit and a duck. (Source here)
These insights are extremely helpful when considering controversial issues in our own day. Take the issue of intelligent design, for example. During the rise of science, scholars worked with paradigms that were able to handle the concept of design in nature - and they found it everywhere. With the secularising influences of the Enlightenment came an acceptance of Deism - so design was admitted only as long as it was pushed to the beginnings of natural history. Later came the rise of materialism and naturalism and the desire to redefine science exclusively in terms of natural causation, and this has led us to the evolutionary world view and the rigid exclusion of intelligent design from science. These paradigm changes were accompanied by a failure to understand scholars with a different paradigm: hence the representation of anyone who upholds intelligent design as an advocate of anti-science and superstition.
The Kuhnian analysis is itself under fire today from people who are deeply influenced by the materialist world view. They cling to positivist emphases with a passion that is looking more and more like religious fervour. However, it is good to read this review in Nature. There are certainly areas of disagreement with Kuhn, but let us not lose sight of his masterful and insightful approach.
"Nevertheless, we may still admire Kuhn's dexterity in broaching challenging ideas with a fascinating mix of examples from psychology, history, philosophy and beyond. We need hardly agree with each of Kuhn's propositions to enjoy - and benefit from - this classic book."
In retrospect: The Structure of Scientific Revolutions
Nature, 484, 164-166 (12 April 2012) | doi:10.1038/484164a
David Kaiser marks the 50th anniversary of an exemplary account of the cycles of scientific progress.
The Structure of Scientific Revolutions: 50th Anniversary Edition
Thomas S. Kuhn (with an introduction by Ian Hacking) Univ. Chicago Press: 2012. 264 pp. ISBN: 9780226458113
The quest for the Higgs boson has been headline news in the world's media, perhaps owing more to its nickname (the "God particle") than to public understanding of why it is so significant. What is not in doubt is that this attention is good for physics and good for science. With so much attention given to technology exploitation, it is important to remind ourselves that fundamental science provides the foundations for advances in technology - and we still need blue-sky research. The excitement surrounding the Higgs boson stimulated a reflective essay in Nature from science writer Heidi Ledford. The question she addresses is: "What fundamental discoveries in biology might inspire the same thrill?"
"We put the question to experts in various fields. Biology is no stranger to large, international collaborations with lofty goals, they pointed out - the race to sequence the human genome around the turn of the century had scientists riveted. But most biological quests lack the mathematical precision, focus and binary satisfaction of a yes-or-no answer that characterize the pursuit of the Higgs. "Most of what is important is messy, and not given to a moment when you plant a flag and crack the champagne," says Steven Hyman, a neuroscientist at the Broad Institute in Cambridge, Massachusetts. Nevertheless, our informal survey shows that the field has no shortage of fundamental questions that could fill an anticipatory auditorium. These questions concern where and how life started - and why it ends.""
The topics identified are worthy of further thought: there are serious issues that need to be explored relating to the proposed three fundamental questions. The first of these is concerned with exobiology and where life originated. The search for signs of extraterrestrial life has been a feature of so many space exploration projects. The past year has witnessed sustained interest in the string of media reports about so-called "Earth-like planets" discovered by the Kepler Mission (comment on the first rocky planet is here). This, plus on-going discussion of solar system probes, plus the possibility of discovering unusual life-forms on Earth, has the goal of finding data to inform responses to the first biological Higgs question.
"The search for extraterrestrial life can be described as one way to test "a standard model of biology", says astrobiologist Chris McKay of the NASA Ames Research Center in Moffett Field, California. "It's the model of DNA and amino acids and proteins and a genetic code," he says. "It's the common features of all biology, and the framework through which everything we know about life is based." If life fundamentally different from this standard model - perhaps relying on a wildly different biochemistry - were found on another planet, it would show that there is more than one way to produce a living system, he adds."
The second big question is "how familiar life originated on Earth". It would appear that panspermia is not currently perceived as part of the story, but the quest is "how to synthesize an evolving, replicating system from scratch". We are back to the primordial soup or something very like it (but see here). The RNA World approach is the front-runner in the minds of most researchers. RNA can encode information and catalyse chemical reactions, but researchers are working with the hypothesis that RNA could replicate itself to make possible an evolutionary pathway. Ledford interviewed Gerald Joyce of the Scripps Research Institute in La Jolla, California.
"In 2009, a paper from Joyce's lab reported the development of a system of RNA molecules that undergo self-sustaining Darwinian evolution. But enzymes and a human hand were needed to create the RNA sequences to start off the reaction, Joyce says, and so far his lab has not found conditions that would allow the system to form spontaneously. "We're still a bit challenged," he says. "But the system is running more and more efficiently all the time.""
Over and over again, it has been shown that while particular pathways of chemical evolution (abiogenesis) can be demonstrated in the lab, the reactions always need the equivalent of "enzymes and a human hand" to yield any products of interest. There are hints that these repeated failures to achieve a viable RNA World are leading to a change of direction.
"Some believe that RNA may have had a precursor. Ramanarayanan Krishnamurthy at the Scripps Research Institute, is testing novel polymers of organic chemicals that could have formed in the primordial goo, in search of those that could replicate and evolve. "RNA was not the first living entity," says Bada. "It's too complex. Something preceded RNA, and that's where the interest is right now.""
Turning to the third big question, can ageing be delayed? Higgs-like expansions of this question are: "why do we age; what pathways control it; and what are the consequences if they are switched off?" For many years, the consensus has been that the biological networks that influence ageing are highly complex and that simple interventions would achieve very little. However, Ledford draws attention to work where the mutation of a single gene in a nematode worm was successful in extending the lifespan of the organism, and another single gene mutation in mice that achieved the same outcome. Such discoveries certainly stimulate hype, but the realists in the research community know that a breakthrough is not just around the corner.
"Ageing, however, "is almost the complete inverse of the situation of the Higgs particle", reflects Thomas Kirkwood, a leader in the field at Newcastle University, UK. "Everything that we're learning tells us it's highly unlikely that we'll find a single unitary cause.""
All three of these proposals for a "biological Higgs" reveal tensions between the mind-set of the researchers and the labyrinthine complexities of the real world. The problem for the researchers is that the information-rich systems they are studying cannot be reduced to simple physics and chemistry. Until the significance of information is grasped, these research programmes will continue to flounder - despite valiant attempts to keep them alive by spinning apparent successes. Information must be recognised as a substantial entity for understanding biological systems. It is not satisfactory to invent scenarios about information being produced by natural selection acting on molecular systems - we need testable hypotheses, not story-telling.
When information issues are accepted as crucial to the science of biology, we might propose an amended trio of biological Higgs: what makes one egg turn into a fly and another into a horse? Why are we conscious? Can ageing be delayed?
And biologists should not be too keen to envy physicists - who themselves have a problem of seeking a reductionist "Theory of Everything". The search for the Higgs boson may be too closely linked to thinking that the Standard Model is the last word on the subject. Whatever the outcome, physicists are just beginning to scratch the surface in their analysis of fundamental particles. Remember, gravity is still a mystery!
The biological Higgs
Nature, 483, 528-530, (29 March 2012) | doi:10.1038/483528a
From the opening paragraphs: Biologists may have little cause to envy physicists - they generally enjoy more generous funding, more commercial interest and more popular support. But they could have been forgiven a moment of physics envy last December when, after a week of build-up and speculation, researchers at the Large Hadron Collider (LHC) near Geneva in Switzerland addressed a tense, standing-room-only auditorium. Scientists there had caught the strongest hints yet of the Higgs boson: what some have called the 'God particle' and the final missing piece of the standard model that explains the behaviour of subatomic particles. [. . .] All this led Nature to wonder: what fundamental discoveries in biology might inspire the same thrill? We put the question to experts in various fields.
The DNA code is made up of codons (3-letter words) derived from 64 different arrangements of bases linking the two DNA strands. Yet these 64 combinations code for only 20 amino acids and a stop signal (as set out here). Thus, different codons are able to produce the same amino acid. The phenomenon is described as the genetic code having "redundancy". In the early years of molecular biology, this redundancy was perceived as an evolutionary accident, unworthy of detailed research but fortunate because it meant that any damaging effects of point mutations were cushioned. However, the evidence has been accumulating that "redundancy" is a misleading word.
"Scientists have known about this redundancy for 50 years, but in recent years, as more and more genomes from creatures as diverse as domestic dogs to wild rice have been decoded, scientists have come to appreciate that not all redundant codons are equal. Many organisms have a clear preference for one type of codon over another, even though the end result is the same. This begged the question the new research answered: if redundant codons do the same thing, why would nature prefer one to the other?" (Source here)
The ribosome in action in protein translation, assembling (and then completing) a protein step by step [=algorithmically] based on the sequence of three-letter codons in the mRNA tape and using tRNA's as amino acid "taxis" and position-arm tool-tips, implementing a key part of a von Neumann-type self replicator (Source here)
New research into protein synthesis in bacteria has shone new light on these issues. "A hidden and never before recognized layer of information in the genetic code has been uncovered by a team of scientists" using a technique called ribosome profiling. This tool allows gene activity inside living cells to be monitored, including the speed with which proteins are made.
"Ribosome profiling takes account of gene activity by pilfering from a cell all the molecular machines known as ribosomes. Typical bacterial cells are filled with hundreds of thousands of these ribosomes, and human cells have even more. They play a key role in life by translating genetic messages into proteins. Isolating them and pulling out all their genetic material allows scientists to see what proteins a cell is making and where they are in the process. Weissman and Li were able to use this technique to measure the rate of protein synthesis by looking statistically at all the genes being expressed in a bacterial cell." (Source here)
Ribosomes bind to mRNA strands and produce protein products. To do this, they have to "read" the sequence of bases and translate them into the sequence of amino acids that make up the protein. The starting point is an AUG codon. However, AUG sequences can appear elsewhere along the mRNA strand so a mechanism is needed to establish whether the AUG codon is the starting point or just a part of the coding sequence. Prokaryotes make extensive use of the Shine-Dalgarno sequence (SD sequence) within the mRNA located near the start codon. The SD sequence forms a strong bond with an anti-Shine-Dalgarno sequence in the ribosome. Consequently, once the SD-aSD bond is formed, the ribosome can readily locate the correct starting point for synthesising the protein.
The key point emerging from the new research is that "redundancy" affecting SD sequences were found to affect the rate of translation.
"By measuring the rate of protein production in bacteria, the team discovered that slight genetic alterations could have a dramatic effect. This was true even for seemingly insignificant genetic changes known as "silent mutations," which swap out a single DNA letter without changing the ultimate gene product. To their surprise, the scientists found these changes can slow the protein production process to one-tenth of its normal speed or less. [. . .] [T]he speed change is caused by information contained in what are known as redundant codons - small pieces of DNA that form part of the genetic code. They were called "redundant" because they were previously thought to contain duplicative rather than unique instructions. This new discovery challenges half a century of fundamental assumptions in biology." (Source here)
What has been discovered is that the genetic code not only has information about the sequence of amino acids, but also about the rate at which the translational machinery carries out its work. The information is about process as well as content.
"What the scientists hypothesize is that the pausing exists as part of a regulatory mechanism that ensures proper checks - so that cells don't produce proteins at the wrong time or in the wrong abundance." (Source here)
The implications of this work go far beyond bacteria. Redundancy is the wrong word! What we have here is another level of information that needs to be part of ongoing research. Are these better understood as regulatory variants? Cornelius Hunter has drawn attention to the erroneous presumption of evolutionists:
"For evolutionists this redundancy was just another biological kludge revealing nature's dysteleology. Their natural expectation was that mutations that produced no change in the amino acid sequence - the so-called synonymous mutations - would be worthless and discarded by evolution. The massive change required by evolution would come about by altering the amino acid sequences of proteins, and so the gene comparisons between species would mostly reveal mutations that did produce different amino acids - the so-called nonsynonymous mutations. It was yet another in a long line of failed expectations. In fact gene comparisons between different species [. . .] revealed that non synonymous sites are disproportionately more conserved than synonymous sites, sometimes by as much as an order of magnitude or more." (Source here)
Another blog post has raised questions about the way molecular data has been used to defend common descent. With this new understanding of the functionality of "redundant" codons, the argument must be re-visited.
"The observation that silent synonymous base-pair substitutions can be of functional relevance to gene expression may undercut an argument made often in support of common descent - that is, the argument that, in genes shared between different taxa, a higher frequency of shared synonymous (assumed to be functionally insignificant) substitutions, than would be predicted under the assumption of neutral evolution, necessarily implies common ancestry." (Source here)
If evolutionary theorists have erred in presuming the variants are meaningless apart from tracing evolutionary lineages, what paradigm could help us move forward? The answer is a paradigm that presumes functionality and keeps searching for functionality within the architecture of living cells. The Design paradigm is capable of doing this - what is needed is less polemic from those who are hostile to design and a greater appreciation that biology as a discipline suffers when design issues are not addressed fairly and openly in scientific discourse.
The anti-Shine-Dalgarno sequence drives translational pausing and codon choice in bacteria
Gene-Wei Li, Eugene Oh and Jonathan S. Weissman
Nature, 484, 538-541, (26 April 2012) | doi:10.1038/nature10965
Protein synthesis by ribosomes takes place on a linear substrate but at non-uniform speeds. Transient pausing of ribosomes can affect a variety of co-translational processes, including protein targeting and folding. These pauses are influenced by the sequence of the messenger RNA. Thus, redundancy in the genetic code allows the same protein to be translated at different rates. However, our knowledge of both the position and the mechanism of translational pausing in vivo is highly limited. Here we present a genome-wide analysis of translational pausing in bacteria by ribosome profiling - deep sequencing of ribosome-protected mRNA fragments. This approach enables the high-resolution measurement of ribosome density profiles along most transcripts at unperturbed, endogenous expression levels. Unexpectedly, we found that codons decoded by rare transfer RNAs do not lead to slow translation under nutrient-rich conditions. Instead, Shine-Dalgarno-(SD)-like features within coding sequences cause pervasive translational pausing. Using an orthogonal ribosome possessing an altered anti-SD sequence, we show that pausing is due to hybridization between the mRNA and 16S ribosomal RNA of the translating ribosome. In protein-coding sequences, internal SD sequences are disfavoured, which leads to biased usage, avoiding codons and codon pairs that resemble canonical SD sites. Our results indicate that internal SD-like sequences are a major determinant of translation rates and a global driving force for the coding of bacterial genomes.
New Layer of Genetic Information Helps Determine How Fast Proteins Are Produced, ScienceDaily (28 March 2012)
A New Study Adds Further Depth to the Information Story, by Jonathan M. (Evolution News & Views, 30 March 2012)
Hunter, C. Here's What That New UCSF Paper Says in Plain English (And Why Evolution Needs Another Do-Over) (Darwin's God, 31 March 2012)
Hunter, C. Here is a Completely Different Way of Doing Science, (Darwin's God, 1st April 2012)
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